Differences in adverse drug reactions in phase III and phase IV of the drug evaluation process.

The study of medications in routine use is called "Phase IV" of the drug evaluation process. Information gathered about drugs in Phases I through III does not provide a sufficient basis for final conclusions about the clinical value of medications after marketing. Changes in preferred indications, patient characteristics (e.g., multimorbidity), treatment mode, or treatment setting in routine as compared to controlled scientific studies lead to changes in causes, incidence, prevalence, predictability, meaning, consequences, and cost-benefit ratios of adverse drug reactions (ADRs). Rare but serious ADRs are only one aspect of postmarketing surveillance; other questions are at least as important. In contrast to Phase III, which has a single study design--the controlled, randomized, double-blind study--Phase IV requires different designs for each of the many different questions. Established methodologies include spontaneous reports, stimulated spontaneous reports, comprehensive observation studies, Phase IV intervention studies, case control studies, prescription event record linkage, and data bank comparisons.